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Background We explored the utility of a small multi-gene DNA panel for assessing molecular profiles of thyroid nodules and influencing clinical decisions by comparing outcomes between tested and untested nodules. Methods Between April 2022 and May 2023, we prospectively performed fine-needle aspiration (FNA) with gene testing via DNA panel of 11 genes (BRAF, RAS [NRAS, HRAS, KRAS], EZH1, DICER1, EIF1AX, PTEN, TP53, PIK3CA, TERT promoter) in 278 consecutive nodules (panel group). Propensity score-matching (1:1) was performed with 475 nodules that consecutively underwent FNA without gene testing between January 2021 and December 2021 (control group). Results In the panel group, positive call rate for mutations was 41.7% (BRAF 16.2%, RAS 12.6%, others 11.5%, double mutation 1.4%) for all nodules, and 40.0% (BRAF 4.3%, RAS 19.1%, others 15.7%, double mutation 0.9%) for indeterminate nodules. Benign call rate was 69.8% for all nodules, and 75.7% for indeterminate nodules. In four nodules, additional TP53 (in addition to BRAF or EZH1) or PIK3CA (in addition to BRAF or TERT) mutations were co-detected. Sensitivity, specificity, positive predictive value, and negative predictive value were 80.0%, 53.3%, 88.1%, 38.1% for all nodules, and 78.6%, 45.5%, 64.7%, 62.5% for indeterminate nodules, respectively. Panel group exhibited lower surgical resection rates than the control group for all nodules (27.0% vs. 52.5%, P

Background: We present the initial outcomes of transoral robotic parathyroidectomy (TORP) using the transoral vestibular approach in patients with primary hyperparathyroidism (PHPT). Method: A retrospective case series analysis was performed on patients diagnosed with PHPT between October 2016 and July 2019 who underwent transoral robotic surgery for parathyroidectomy. Results: Thirteen patients (five males and eight females) successfully underwent TORP at our institution from October 2016 to July 2019. Eight patients underwent TORP alone, and five underwent TORP combined with transoral robotic thyroidectomy for papillary thyroid carcinoma. No intra- or postoperative complications were observed. Serum levels of parathyroid hormone, total calcium, and ionized calcium decreased to normal postoperatively and continued to decrease during the follow-up period. Conclusion: This study suggests that TORP holds promise for the treatment of patients with PHPT with the advantages of the robotic procedure, including dynamic visualization and meticulous dissection.

Abstract Robotic adrenalectomy (RA) has gained significant popularity in the management of adrenal gland diseases. We report our experience at a single tertiary institution and evaluate the safety and surgical outcomes of RA. The data of 122 consecutive patients who underwent RA from October 2009 to December 2022 at Korea University Anam Hospital (Seoul, Korea) were reviewed. There were no perioperative complications. Clinicopathological features and surgical outcomes were retrospectively analyzed through complete chart reviews. Noteworthy findings include the influence of sex, tumor size, and body mass index on operation time, with the female and small tumor groups exhibiting shorter operation times (P = 0.018 and P = 0.009, respectively). Pheochromocytoma was identified as a significant independent risk factor for a longer operation time in the multivariate analysis [odds ratio (OR), 3.709; 95% confidence interval (CI), 1.127–12.205; P = 0.031]. A temporal analysis revealed a decreasing trend in mean operation times across consecutive groups, reflecting a learning curve associated with RA adoption. RA is a safe and effective operative technique alternative to laparoscopic adrenalectomy that has favorable surgical outcomes and enhances the convenience of the operation.

Abstract The study investigated the feasibility of robotic bilateral axillo-breast approach (BABA) thyroidectomy for patients with thyroid tumors larger than 4 cm. BABA thyroidectomy has previously shown safety and effectiveness for thyroid surgeries but lacked extensive data on its application to larger tumors. Between October 2008 and August 2022, there were 74 patients underwent robotic BABA thyroidectomy due to thyroid nodules exceeding 4 cm in size. The mean patient age was 40.3 years. Fine needle aspiration results classified the tumors as benign (50.0%), atypia of undetermined significance (27.0%), follicular neoplasm (16.2%), suspicious for malignancy/malignancy (5.4%), or lymphoma (1.4%). The average tumor size was 4.9 cm, with the majority (85.1%) undergoing thyroid lobectomy, and the rest (14.9%) receiving total thyroidectomy. The mean total operation time was 178.4 min for lobectomy and 207.3 min for total thyroidectomy. Transient vocal cord palsy (VCP) was found in 3 patients (4.1%), and there was no permanent VCP. Among patients who underwent total thyroidectomy, transient hypoparathyroidism was observed in three (27.2%), and permanent hypoparathyroidism was observed in one (9.1%). There were no cases of open conversion, tumor spillage, bleeding, flap injury, or tumor recurrence. In conclusion, robotic BABA thyroidectomy may be a safe treatment option for large-sized thyroid tumors that carries no significant increase in complication rates.

Abstract This observational study aimed to compare the glottic view between video and direct laryngoscopy for tracheal intubation in the surgical position for thyroid surgery with intraoperative neuromonitoring. Patients scheduled for elective thyroid surgery with intraoperative neuromonitoring were enrolled. After the induction of anesthesia, patients were positioned in the thyroid surgical posture with a standard inclined pillow under their head and back. An investigator assessed the glottic view using the percentage of glottic opening (POGO) scale and the modified Cormack–Lehane grade in direct laryngoscopy and then video laryngoscopy sequentially while using the same McGRATH™ MAC video laryngoscope at once, with or without external laryngeal manipulation, at the surgical position. A total of thirty-nine patients were participated in this study. Without external laryngeal manipulation, the POGO scale significantly improved during video laryngoscopy compared to direct laryngoscopy in the thyroid surgical position (60.0 ± 38.2% vs. 22.4 ± 23.8%; mean difference (MD) 37.6%, 95% confidence interval (CI) = [29.1, 46.0], P

Abstract Neural network models have been used to analyze thyroid ultrasound (US) images and stratify malignancy risk of the thyroid nodules. We investigated the optimal neural network condition for thyroid US image analysis. We compared scratch and transfer learning models, performed stress tests in 10% increments, and compared the performance of three threshold values. All validation results indicated superiority of the transfer learning model over the scratch model. Stress test indicated that training the algorithm using 3902 images (70%) resulted in a performance which was similar to the full dataset (5575). Threshold 0.3 yielded high sensitivity (1% false negative) and low specificity (72% false positive), while 0.7 gave low sensitivity (22% false negative) and high specificity (23% false positive). Here we showed that transfer learning was more effective than scratch learning in terms of area under curve, sensitivity, specificity and negative/positive predictive value, that about 3900 images were minimally required to demonstrate an acceptable performance, and that algorithm performance can be customized according to the population characteristics by adjusting threshold value.

Abstract We evaluated the pre- and postoperative sleep quality of patients with newly diagnosed papillary thyroid carcinoma (PTC) who underwent thyroid surgery, and investigated the factors associated with persistent poor sleep quality. The Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale, and Stanford sleepiness scale were used to estimate sleep quality and daytime sleepiness. Face-to-face surveys were conducted preoperatively, and 1, 4, and 10 months after thyroid surgery. The PSQI was administered during a telephone interview about after 5 years after surgery. Forty-six patients (mean age 47.3 ± 10.1 years) with PTC (11 males, 35 females) were included in this study. Twenty-one participants underwent lobectomy and 25 underwent total thyroidectomy. Preoperatively, 35 (76.1%) patients showed poor sleep quality. PSQI scores at postoperative 1, 4, and 10 months were significantly lower than preoperative scores (p

Abstract This prospective, randomized controlled trial evaluated the effect of neostigmine for intraoperative neuromonitoring (IONM) during thyroid surgery. Forty subjects undergoing thyroidectomy with IONM, randomized into neostigmine administration after tracheal intubation (Group N, n = 20) or control treatment with normal saline (Group C, n = 20), completed the trial. Electromyography amplitudes of the vagus nerve (V1) were recorded before thyroid dissection. The time from the initial V1 signal check to successful V1 stimulation was recorded. In Group N, all the patients had a successful V1 signal at the first check, whereas ten (50%) patients in Group C had a time delay between the initial V1 check and successful V1 (p

Background: Hypoxia is a well-recognized characteristic of the tumor microenvironment of solid cancers. This study aimed to analyze hypoxia-related genes shared by groups based on tumor location. Methods: A total of 9 hypoxia-related pathways from the Kyoto Encyclopedia of Genes and Genomes database or the Reactome database were selected, and 850 hypoxia-related genes were analyzed. Based on their anatomical locations, 14 tumor types were categorized into 6 groups. The group-specific genetic risk score was classified as high- or low-risk based on mRNA expression, and survival outcomes were evaluated. Results: The risk scores in the Female Reproductive group and the Lung group were internally and externally validated. In the Female Reproductive group, CDKN2A, FN1, and ITGA5 were identified as hub genes associated with poor prognosis, while IL2RB and LEF1 were associated with favorable prognosis. In the Lung group, ITGB1 and LDHA were associated with poor prognosis, and GLS2 was associated with favorable prognosis. Functional enrichment analysis showed that the Female Reproductive group was enriched in relation to cilia and skin, while the Lung group was enriched in relation to cytokines and defense. Conclusions: This analysis may lead to better understanding of the mechanisms of cancer progression and facilitate establishing new biomarkers for prognosis prediction.

Objectives. The BRAFV600E mutation is a major driver mutation in papillary thyroid cancer. The aim of this study was to elucidate the correlation between DNA methylation and gene expression changes induced by the BRAFV600E mutation in thyroid cells. Methods. We used Nthy/BRAF cell lines generated by transfection of Nthy/ori cells with the wild-type BRAF gene (Nthy/WT cells) and the V600E mutant-type BRAF gene (Nthy/V600E cells). We performed gene expression microarray and DNA methylation array analyses for Nthy/WT and Nthy/V600E cells. Two types of array data were integrated to identify inverse correlations between methylation and gene expression. The results were verified in silico using data from The Cancer Genome Atlas (TCGA) and in vivo through pyrosequencing and quantitative real-time polymerase chain reaction (qRT-PCR). Results. In the Nthy/V600E cells, 199,821 probes were significantly hypermethylated, and 697 genes showed a “hypermethylation-downregulation” pattern in Nthy/V600E. Tumor suppressor genes and apoptosis-related genes were included. In total, 66,446 probes were significantly hypomethylated, and 227 genes showed a “hypomethylation-upregulation” pattern in Nthy/V600E cells. Protooncogenes and developmental protein-coding genes were included. In the TCGA analysis, 491/697 (70.44%) genes showed a hypermethylation-downregulation pattern, and 153/227 (67.40%) genes showed a hypomethylation-upregulation pattern. Ten selected genes showed a similar methylation-gene expression pattern in pyrosequencing and qRT-PCR. Conclusion. Induction of the BRAFV600E mutation in thyroid cells led to frequent hypermethylation. Anticancer genes, such as those involved in tumor suppression or apoptosis, were downregulated by upstream hypermethylation, whereas carcinogenic genes, such as protooncogenes, were upregulated by hypomethylation. Our results suggest that the BRAFV600E mutation in thyroid cells modulates DNA methylation and results in cancer-related gene expression.

Abstract Intraoperative neuromonitoring (IONM) is frequently used in thyroid surgery to reduce recurrent laryngeal nerve injury. The use of neuromuscular blockade agent to facilitate tracheal intubation, is a common cause of IONM failure. We performed a retrospective analysis to assess the efficacy of neostigmine‐glycopyrrolate as a neuromuscular blockade reversal agent for IONM during thyroid surgery. Rocuronium (0.6 mg/kg) was administered for muscle relaxation. Neostigmine (2 mg) and glycopyrrolate (0.4 mg) were administered immediately after intubation. Cricothyroid muscle‐twitch response upon external branch of superior laryngeal nerve stimulation and electromyography amplitudes of vagal and recurrent laryngeal nerves before (V1, R1) and after thyroid resection (V2, R2) were recorded. Fifty patients (23 males, 27 females) were included in the analysis. The diagnoses comprised 43 papillary thyroid carcinomas and seven benign diseases. The mean time between rocuronium injection and neostigmine‐glycopyrrolate injection was 5.1 ± 1.2 min, and the mean time from neostigmine‐glycopyrrolate injection to successful cricothyroid muscle twitching upon external branch of superior laryngeal nerve stimulation was 21.0 ± 4.5 min. All patients had V1 and R1 amplitudes of more than 500 μV each, with mean V1 and R1 amplitudes of 985.3 ± 471.6 μV and 1177.2 ± 572.7 μV, respectively. Neostigmine‐glycopyrrolate was effectively used as a neuromuscular blockade reversal agent for IONM in thyroid surgeries without a significant increase in bucking events. Administration of neostigmine‐glycopyrrolate immediately after intubation can be recommended for successful NMB reversal to facilitate IONM during thyroid surgery.

Abstract Many patients experience cervical adhesions after thyroid surgery. To date, however, no studies have objectively measured the effects of anti-adhesion agents on cervical adhesion symptoms. This study evaluated the effects of an anti-adhesion agent on cervical adhesions after thyroid surgery, as determined using a system that measures the extent of marker movement objectively. One hundred patients were randomized in a 1:1 ratio to undergo thyroid surgery with or without the anti-adhesion agent Collabarrier. Using specially manufactured recording equipment, the position of the marker on neck skin was measured before surgery, and 2 weeks, 3 months, and 9 months after surgery. Relative change in marker distance, calculated by subtracting the marker position before surgery from the marker positions 2 weeks, 3 months, and 9 months after surgery, differed significantly in the groups of patients who underwent thyroid surgery with and without the anti-adhesion agent (P

Abstract For pheochromocytoma and sympathetic paraganglioma (PPGL), surgery can be used as a curative treatment; however, the life-threatening risk of perioperative hemodynamic instability (HI) presents challenges. This study aimed to analyze the incidence and predictive factors of perioperative HI. The electronic medical records of 114 consecutive patients who underwent surgery for PPGLs at our institution were retrospectively reviewed. HI was defined as one or more episodes of systolic blood pressure > 200 mmHg or mean blood pressure

Background Although smoking is generally carcinogenic, its effect on thyroid cancers is still subject to controversy. The purpose of this study was to summarize the role of smoking in relation to thyroid cancer occurrence. Methods We performed a meta-analysis of 24 eligible studies: 21 case-control studies and three prospective cohort studies. The summary odds ratio (OR) and 95% confidence interval (CI) of all studies were acquired based on random effect model. Further subgroup analyses were conducted according to gender, histological type of thyroid cancer, and smoking status of patients for the case-control studies. Results The summary effect size indicated a negative association of smoking for thyroid cancer (OR, 0.798; 95% CI, 0.681 to 0.935). From the subgroup analyses for the case-control studies, reduced risk of thyroid cancer was observed in both men (OR, 0.734; 95% CI, 0.553 to 0.974) and women (OR, 0.792; 95% CI, 0.700 to 0.897). The protective effect of smoking was observed in studies in which thyroid cancer was limited to differentiated thyroid cancers (DTCs) (OR, 0.798; 95% CI, 0.706 to 0.902). Conclusion Our results suggests that smoking may have a protective effect on thyroid cancer, especially on DTCs. Further studies with larger sample sizes should be conducted in elucidating the dose and time dependent effect of smoking on thyroid cancer with specific focus on the types of thyroid cancers.

BackgroundInducing and reversing neuromuscular block is essential to a positive outcome of thyroid surgery, with intraoperative neuromonitoring (IONM) being used to decrease recurrent and superior laryngeal nerve injuries and improve vocal outcome. Neostigmine is a non-specific broad-spectrum and inexpensive reversal agent for neuromuscular blocking agents (NMBAs). The aim of this porcine study was to explore the effect of neostigmine on electromyography (EMG) signal recovery profile following the commonly used NMBAs, cisatracurium and rocuronium.MethodsTwelve piglets were allocated into two groups with six piglets in each group. When stable baseline EMG signals were obtained, a neuromuscular block was induced by intravenous cisatracurium 0.2 mg/kg (group C) or rocuronium 0.6 mg/kg (group R) for each piglet. We compared laryngeal EMG tracing with spontaneous recovery (control) and neostigmine (0.04 mg/kg) reversal for each group. The time course of real-time laryngeal EMG signals was observed for 30 min from NMBA injection. Effects of neostigmine on EMG signal were assessed at 50% EMG recovery and by the maximum neuromuscular block recovery degree from the baseline value.ResultsNeostigmine shortened the recovery time to 50% EMG amplitude in both group C (16.5 [2.5] vs. 29.0 [2.0] min, P

Background The use of intraoperative neuromonitoring (IONM) in thyroid surgery to preserve recurrent laryngeal nerve (RLN) function has been widely accepted. We aimed to evaluate the usefulness of IONM in reoperation for recurrent thyroid cancer patients to help identify the RLN and prevent vocal cord palsy (VCP). Methods We analyzed 121 consecutive patients (with IONM group, 48 patients; without IONM group, 73 patients) who underwent reoperation for recurrent thyroid cancer after total thyroidectomy from January 2009 to March 2019 in our institution without VCP due to previous operations. Data including age, sex, number of previous operations, histologic subtype of the malignancy at the initial operation, operation time, RLNs at risk, difficulty of RLN identification, surgical procedure, VCP, and other postoperative complications were reviewed. Vocal cord movement evaluations were performed preoperatively and at 2 weeks postoperatively to evaluate RLN function. In patients with VCP, additional evaluations were performed. VCP exceeding 12 months after surgery was considered permanent VCP. Results VCP was observed in six (12.5%) and 16 (21.9%) patients with and without IONM (P=0.189). Transient and permanent VCP were found in three (6.3%) and three (6.3%) patients with IONM (P=0.098 and P=0.982, respectively) versus in 12 (16.4%) and four (5.5%) patients without IONM. Conclusion The incidence of transient VCP seems to be lower in reoperations with IONM; however, there was no statistical significances. Further study will be needed to ascertain the efficacy of IONM in reoperation for recurrent thyroid cancer patients.

Abstract In order to analyze the associations between thyroid cancer and environmental factors, we analyzed the national sample cohort representative of the entire population provided by the Korean National Health Insurance Service database record from 2006 to 2015. The cohort was categorized according to age, body mass index, income, residential areas, frequency of exercise, frequency of alcohol drinking, diet, presence or absence of hyperthyroidism, presence or absence of hypothyroidism, and smoking data. Age ≥ 55 years (HR 0.68, 95% CI 0.53–0.88), lower income (0.57, 0.40–0.80), and current smoking (0.69, 0.55–0.85) were associated with lower thyroid cancer occurrence among men. Body mass index (BMI) ≥ 25 kg/m2 (1.51, 1.26–1.82), higher income (1.44, 1.19–1.76), urban residence (1.24, 1.03–1.49), and presence of hypothyroidism (3.31, 2.38–4.61) or hyperthyroidism (2.46, 1.75–3.46) were associated with higher thyroid cancer occurrence among men. Age ≥ 55 years (0.63, 0.56–0.71), moderate alcohol drinking (0.87, 0.77–0.99), and current smoking (0.56, 0.37–0.85) were associated with lower thyroid cancer occurrence among women. BMI ≥ 25 kg/m2 (1.41, 1.26–1.57), frequent exercise (1.21, 1.07–1.36), higher income (1.18, 1.06–1.32), urban residence (1.17, 1.06–1.29), and presence of hypothyroidism (1.60, 1.40–1.82) or hyperthyroidism (1.38, 1.19–1.61) were associated with higher thyroid cancer occurrence among women. In conclusion, age ≥ 55 years and current smoking were associated with lower thyroid cancer occurrence, while BMI ≥ 25 kg/m2, higher income, urban residence, hypothyroidism, and hyperthyroidism were associated with higher occurrence in both men and women.

BackgroundNeuromuscular blocking agents provide muscular relaxation for tracheal intubation and surgery. However, the degree of neuromuscular block may disturb neuromuscular transmission and lead to weak electromyography during intraoperative neuromonitoring. This study aimed to investigate a surgeon-friendly neuromuscular block degree titrated sugammadex protocol to maintain both intraoperative neuromonitoring quality and surgical relaxation during thyroid surgery.MethodsA total of 116 patients were enrolled into two groups and underwent elective thyroid surgery with intraoperative neuromonitoring. All patients followed a standardized intraoperative neuromonitoring protocol with continuous neuromuscular transmission monitoring and received 0.6 mg/kg rocuronium for tracheal intubation. Patients were allocated into two groups according to the degree of neuromuscular block when the anterior surface of the thyroid gland was exposed. The neuromuscular block degree was assessed by the train-of-four (TOF) count and ratio. Patients in group I received sugammadex 0.25 mg/kg for non-deep neuromuscular block degree (TOF count = 1~4). Patients in group II were administered sugammadex 0.5 mg/kg for deep neuromuscular block degree (TOF count = 0). The quality of the intraoperative neuromonitoring was measured using the V1 electromyography (EMG) amplitude. An amplitude less than 500 μV and greater than 500 μV was defined as weak and satisfactory, respectively.ResultsThe quality of the intraoperative neuromonitoring was not different between groups I and II (satisfactory/weak: 75/1 vs. 38/2, P = 0.14). The quality of surgical relaxation was acceptable after sugammadex injection and showed no difference between groups [55/76 (72.3%) in group I vs. 33/40 (82.5%) in group II, P = 0.23].ConclusionsThis surgeon-centered sugammadex protocol guided by neuromuscular block degree (0.5 mg/kg for deep block and 0.25 mg/kg for others) showed comparably high intraoperative neuromonitoring quality and adequate surgical relaxation. The results expanded the practicality of sugammadex for precise neuromuscular block management during monitored thyroidectomy.

Abstract Background Upregulation of SLC2A genes that encode glucose transporter (GLUT) protein is associated with poor prognosis in many cancers. In colorectal cancer, studies reporting the association between overexpression of GLUT and poor clinical outcomes were flawed by small sample sizes or subjective interpretation of immunohistochemical staining. Here, we analyzed mRNA expressions in all 14 SLC2A genes and evaluated the association with prognosis in colorectal cancer using data from the Cancer Genome Atlas (TCGA) database. Methods In the present study, we analyzed the expression of SLC2A genes in colorectal cancer and their association with prognosis using data obtained from the TCGA for the discovery sample, and a dataset from the Gene Expression Omnibus for the validation sample. Results SLC2A3 was significantly associated with overall survival (OS) and disease-free survival (DFS) in both the discovery sample (345 patients) and validation sample (501 patients). High SLC2A3 expression resulted in shorter OS and DFS. In multivariate analyses, high SLC2A3 levels predicted unfavorable OS (adjusted HR 1.95, 95% CI 1.22–3.11; P = 0.005) and were associated with poor DFS (adjusted HR 1.85, 95% CI 1.10–3.12; P = 0.02). Similar results were found in the discovery set. Conclusion Upregulation of the SLC2A3 genes is associated with decreased OS and DFS in colorectal cancer patients. Therefore, assessment of SLC2A3 gene expression may useful for predicting prognosis in these patients.

Hypothyroidism is a recognized sequela of conventional thyroid lobectomy. However, there have been no studies on the incidence of hypothyroidism following the preservation of the isthmus and pyramid during lobectomy. Therefore, in the present study, we compared the incidence of hypothyroidism following conventional lobectomy and lobectomy during which the isthmus and pyramidal lobe were preserved. Data for a total of 65 patients collected between September 2018 and April 2019 were reviewed retrospectively. Circulating thyroid-stimulating hormone (TSH) concentration was measured before and after surgery in a group who underwent conventional thyroid lobectomy (n = 29) and in a group in which the isthmus and pyramid were preserved (n = 36). We found no significant difference in TSH concentration between the two groups before surgery, or 3 months or 1 year after surgery. Thus, there might be no difference in the incidence of postoperative hypothyroidism between patients who undergo conventional thyroid lobectomy and those in which the isthmus and pyramid are preserved.

Objective. Stimulator-attached dissecting instruments are useful for intraoperative nerve monitoring during thyroidectomy. The aim of this study was to evaluate the feasibility of an attachable ring stimulator (ARS) by comparing the electromyography (EMG) amplitudes evoked by an ARS and a conventional stimulator. Methods. Medical records of fourteen patients who underwent thyroidectomy using intraoperative neuromonitoring between June and August 2019 were retrospectively reviewed. The amplitudes of V1, R1, R2, and V2 signals were checked using both the ARS and a conventional stimulator, at the same point. Results. Both stimulators were tested on 20 recurrent laryngeal nerves (RLNs) and 20 vagus nerves (VNs). In all the nerves, the amplitudes of V1, R1, R2, and V2 were greater than 500 μV. The mean amplitudes of V1, R1, R2, and V2 checked with the ARS were 1175, 1432, 1598, and 1279 μV, respectively. The mean amplitudes of V1, R1, R2, and V2 checked with the conventional stimulator were 1140, 1425, 1557, and 1217 μV, respectively. Difference between amplitudes evoked by the two stimulators for V1, R1, R2, and V2 was 77, 110, 102, and 99 μV, respectively. There was no statistical difference in the amplitudes between the two groups for V1, R1, R2, and V2. Conclusion. The ARS transferred electric stimulation as effectively as the conventional stimulator. It is an effective tool for repeated stimulation and facilitates continuous feedback regarding the functional integrity of nerves during thyroid surgery.

ObjectivesAugmented reality (AR) technology has become rapidly available and is suitable for various medical applications since it can provide effective visualization of intricate anatomical structures inside the human body. This paper describes the procedure to develop an AR app with Unity3D and Vuforia software development kit and publish it to a smartphone for the localization of critical tissues or organs that cannot be seen easily by the naked eye during surgery.MethodsIn this study, Vuforia version 6.5 integrated with the Unity Editor was installed on a desktop computer and configured to develop the Android AR app for the visualization of internal organs. Three-dimensional segmented human organs were extracted from a computerized tomography file using Seg3D software, and overlaid on a target body surface through the developed app with an artificial marker.ResultsTo aid beginners in using the AR technology for medical applications, a 3D model of the thyroid and surrounding structures was created from a thyroid cancer patient's DICOM file, and was visualized on the neck of a medical training mannequin through the developed AR app. The individual organs, including the thyroid, trachea, carotid artery, jugular vein, and esophagus were localized by the surgeon's Android smartphone.ConclusionsVuforia software can help even researchers, students, or surgeons who do not possess computer vision expertise to easily develop an AR app in a user-friendly manner and use it to visualize and localize critical internal organs without incision. It could allow AR technology to be extensively utilized for various medical applications.

Background and Objectives: Robotic thyroidectomy via the bilateral axillo-breast approach (BABA), first introduced in Korea in 2008, has become a standard method of thyroid removal worldwide. The introduction of robotic surgical systems has enabled more patients to benefit from BABA robotic thyroidectomy, with good postoperative and excellent cosmetic results. To date, no studies have compared the benefits of the four currently available da Vinci robotic systems (S, Si, X, and Xi) for BABA robotic thyroidectomy. To determine the da Vinci model most suitable for BABA robotic thyroidectomy, the present study compared the perioperative outcomes in patients who underwent BABA robotic thyroidectomy using the four da Vinci models. Materials and Methods: This retrospective study evaluated outcomes in patients (n = 750) who underwent BABA robotic thyroidectomy using the four da Vinci systems from 2013 to 2019. The clinicopathologic data, including operation time, were compared. Substudy A compared the da Vinci models S and Si from 2013 to 2017, and substudy B compared models Si, X, and Xi from 2018 to 2019. Results: Substudy A, comparing the da Vinci S and Si systems, found no statistically significant differences between the two groups, whereas substudy B found that operation time was shorter in patients who underwent BABA robotic thyroidectomy with the da Vinci Xi system than with the Si and X systems. Conclusions: The da Vinci model Xi system can benefit patients undergoing BABA robotic thyroidectomy by shortening the operation time.

Background and Objectives: Preserving the recurrent laryngeal nerve (RLN) is important in thyroid surgery. However, no standardized surgical method for locating the RLN has been established. We defined a new anatomical definition termed “lower central triangle” (LCT) for consistent identification of RLN and used intraoperative nerve monitoring (IONM) to aid in identification and dissection of RLN. Materials and Methods: Patients undergone thyroidectomy were reviewed retrospectively in Seoul National University Bundang Hospital from January to September 2017. Patients with papillary thyroid carcinoma, follicular neoplasm, and Graves’ Disease were included while right side non-RLN in arteriosus lusoria, cancer invasion, pre-existing vocal cord palsy, or under the age of 18 were excluded. RLNs were tested with IONM within LCT consisting of the lower pole as the apex and the common carotid artery as the opposite side. The samples were divided into two groups, IONM and non-IONM. Results: Forty lobes in total were included, 22 in IONM group and 18 in non-IONM group. Groups were not significantly different in age, cancer proportion, and accompanying thyroiditis while sex and nodule size differed. RLN detection time was 10.43 s shorter (p < 0.001), and confirmation time was 10.67 s shorter (p = 0.09) in IONM group than in non-IONM group. Both right and left RLNs were located predominately in the middle of LCT. No transient or permanent vocal cord palsy occurred. Conclusions: While IONM is an appropriate aid for thyroidectomy, our approach using LCT to locate the RLN is a novel definition of anatomy that provides prompt identification of the RLN in thyroid surgery.

The purpose of this study was to assess the relationship between vitamin D receptor gene (VDR) expression and prognostic factors in papillary thyroid cancer (PTC). mRNA sequencing and somatic mutation data from The Cancer Genome Atlas (TCGA) were analyzed. VDR mRNA expression was compared to clinicopathologic variables by linear regression. Tree-based classification was applied to find cutoff and patients were split into low and high VDR group. Logistic regression, Kaplan–Meier analysis, differentially expressed gene (DEG) test and pathway analysis were performed to assess the differences between two VDR groups. VDR mRNA expression was elevated in PTC than that in normal thyroid tissue. VDR expressions were high in classic and tall-cell variant PTC and lateral neck node metastasis was present. High VDR group was also associated with classic and tall cell subtype, AJCC stage IV and lower recurrence-free survival. DEG test reveals that 545 genes were upregulated in high VDR group. Thyroid cancer-related pathways were enriched in high VDR group in pathway analyses. VDR mRNA overexpression was correlated with worse prognostic factors such as subtypes of papillary thyroid carcinoma that are known to be worse prognosis, lateral neck node metastasis, advanced stage and recurrence-free survival.

Background: Among several minimally invasive adrenalectomy techniques, lateral transperitoneal adrenalectomy (LTA) is the procedure of choice for benign adrenal tumors; however, posterior retroperitoneoscopic adrenalectomy (PRA) is an alternative that is increasing in popularity. This study compared the outcomes of these two approaches. Methods: Since a single surgeon started adrenalectomy, LTA had been performed exclusively until PRA was adopted and became the standard treatment. Therefore, the consecutive patients were allocated into two groups according to the date of surgery: the first group received LTA and the second group received PRA. Results: LTA was performed in 29 patients and PRA in 19 patients. There was no difference in sex, age, body mass index, clinical diagnosis, and tumor size between the LTA and the PRA group. The PRA group showed less blood loss (117.0 mL vs. 58.5 mL, p = 0.035) and tended to have a shorter operating time (92.2 minutes vs. 78.1 minutes, p = 0.054) and less pain score on postoperative Day 1 (3.8 vs. 3.0, p = 0.095) and Day 2 (3.2 vs. 2.5, p = 0.051). The mean operation time was significantly shorter for patients in the PRA group undergoing right adrenalectomy (109.2 minutes vs. 80.5 minutes, p = 0.009), but those undergoing left adrenalectomy had a similar operating time to the LTA group (83.2 minutes vs. 74.8 minutes, p = 0.380). Conclusion: PRA is a good alternative operative technique for an endocrine surgeon who is experienced in the transperitoneal approach.

Background and objectives: The study assesses quality of life (QoL) in patients who underwent thyroidectomy compared to the general population. Materials and Methods: QoL data from post-thyroidectomy patients and individuals with no subjective health concerns, who had attended a routine health screening visit, were evaluated. QoL was assessed using the modified version of Korean Short Form 12 questionnaire (SF-12). Patients and controls were matched using the propensity score approach and a ratio of 1:4. Results: Data from a total of 105 patients and 420 controls were analyzed. For five SF-12 items, lower QoL was found in patients (p < 0.05). Multivariate analysis revealed that a follow-up duration of 50 years were independent risk factors. No significant difference was found between controls and patients who were >1-year post-surgery. Conclusions: For specific SF-12 items, QoL was lower in post-thyroidectomy patients than in controls. No intergroup difference in QoL was found >1-year post-surgery.

Background and objectives: Currently, few studies have been conducted on postoperative chylothorax, specifically in total thyroidectomy with modified radical neck dissection (MRND) in papillary thyroid carcinoma patients. This study provides the actual incidence, etiology, and clinical features of postoperative chylothorax and reports the clinical outcomes after treatment, which were dependent upon the severity of the complications. Materials and Methods: The medical charts of 111 papillary thyroid cancer (PTC) patients who underwent total thyroidectomy with modified radical neck dissection from January 2016 to December 2018 were reviewed retrospectively. The results were compared in three groups: the no chylothorax group, the subclinical (asymptomatic) group, and the clinical (symptomatic) group. Results: Chylothorax occurred in 23 patients (20.7%, 23/111). Nineteen (82.6%, 19/23) were subclinical chylothorax cases, which implies a small amount of chyle leakage with no respiratory symptoms. Four (17.4%, 4/23) were clinical, meaning they had either respiratory symptoms, such as dyspnea, desaturation, or a large amount of chylothorax in the images. The incidence was significantly higher in patients who underwent left modified radical neck dissection, and this corresponds to the side in which chylothorax occurred. There were also statistical differences in the drainage color, peak amount, or drain removal time. Conclusions: Postoperative chylothorax is a rare complication following neck dissection. However, it can be fatal if the condition progresses. Therefore, patients who undergo total thyroidectomy with modified radical neck dissection, especially on the left side, should be monitored for respiratory symptoms, and serial chest x-ray images obtained.

The aim of this study was to evaluate preoperatively identifiable clinical and ultrasonographic characteristics associated with central lymph node metastasis (CLNM) in clinically node negative papillary thyroid carcinoma (PTC) patients. Records of the patients who underwent thyroidectomy with prophylactic central lymph node dissection due to clinically node negative PTC (size, 1.0-3.0 cm) were reviewed. Of a total of 174 patients, 71 (40.8%) had CLNMs. CLNM was more associated with capsule invasion than capsule non-invasion on ultrasonography (68.4% vs. 37.4%, p = 0.009). In the 155 patients without capsule invasion, a distance from the capsule < 1.9 mm was associated with CLNM in univariable (p = 0.002) and multivariable analysis (p < 0.001). Any PTC patient with a distance from the capsule ≥ 1.9 mm did not have CLNM whereas 40.8% (58/142) of PTC patients with a distance from the capsule < 1.9 mm had CLNM. CLNM was not associated with age, gender, or tumor size on ultrasonography. Distance from capsule ≥ 1.9 mm on preoperative ultrasonography was a significant indicator for not having CLNM in clinically node negative PTC patients. Measuring distance from the capsule on preoperative ultrasonography images could help select patients with PTC who could benefit from prophylactic central lymph node dissection.

Pheochromocytoma and paraganglioma are tumors of neuroectoderm origin. Up to 40% of patients with these tumors have germline mutations in known susceptibility genes. We report a novel RET germline mutation (exon 15; c.2692G>T (D898Y)) in a pheochromocytoma patient, as well as in her two asymptomatic sons and older sister. A 49-year-old female came to our clinic presenting with a right adrenal gland mass detected during a healthcare examination. Her mother and two sisters had previously undergone thyroidectomy for papillary thyroid carcinomas. The levels of vanillylmandelic acid and other catecholamines were elevated in 24-hour urine, and an imaging study revealed a right adrenal mass. She underwent laparoscopic adrenalectomy and the final pathologic diagnosis was pheochromocytoma. Mutation screening detected a RET p.D898Y mutation, both in the patient and in the patient’s two sons and older sister. This is the first description of a RET D898Y mutation in a pheochromocytoma patient and her family. The mutation should be categorized as a variant of unknown significance because no RET gene related disorders were detected in this family. Long term follow-up will be required to determine the clinical significance of the RET D898Y mutation.

The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN). A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of the proposed method as an automated white blood cell differential count system.

Since the adoption of the Da Vinci robotic system for remote access thyroid surgery, robotic thyroidectomy (RT) has become a popular surgical option for patients who want to avoid neck scars. Surgeons in South Korea pioneered this surgical technique and have reported successful outcomes. Although many studies have reported that RT is a feasible and safe therapeutic alternative, concerns over the surgical and oncological safety of RT remain. This article reviews the advantages and disadvantages of RT and compares the surgical safety and oncological completeness of RT with conventional open thyroidectomy.

Purpose: Laparoscopic adrenalectomy has been a standard method for adrenal gland tumors. On the other hand, hand-assisted laparoscopic adrenalectomy is an operative method which enables operator to use a hand to facilitate dissection and retraction. The aim of this study was to report initial experience of hand-assisted laparoscopic adrenalectomy and to evaluate potentialities for surgical application. Methods: Seven patients who underwent hand-assisted adrenalectomy from September 2010 to July 2013 were enrolled. Clinicopathological characteristics, intraoperative hemodynamic status, and parameters associated with postoperative recovery were reviewed. Surgical indications for hand-assisted laparoscopic adrenalectomy were right side adrenal tumors larger than 4 cm on preoperative computed tomography (CT) scan. Mean age was 36.9 years (range, 23 to 51 years) and there were 3 men and 4 women. Results: The mean size of adrenal tumor was 6.1±2.4 cm. Operation time was 119.4±29.7 minutes in average and mean blood loss was 142.9±109.7 mL. There were 4 patients with pheochromocytoma, one patient for each adrenocortical neoplasm, paraganglioma and lymphoma. Intraoperative hypertensive crisis were observed in 2 patients with pheochromocytoma and there was no intraoperative tachycardia crisis. Patients had first oral intake at 1.4±0.8 days in average and mean postoperative hospital stay was 3.4±1.3 days. There was no postoperative complication and mortality. The median follow-up was 12 months and there was no case with evidence of recurrence during the periods. Conclusion: In our initial experience, hand-assisted laparoscopic adrenalectomy was performed safely and effectively. Hand-assisted laparoscopic adrenalectomy might be an alternative to laparoscopic adrenalectomy for moderate sized right side adrenal tumors.

BACKGROUND:This study evaluated the effects of acute high-dose and chronic lifetime exposure to alcohol and exposure patterns on the development of differentiated thyroid cancer (DTC). METHODS:The Thyroid Cancer Longitudinal Study (T-CALOS) included 2,258 DTC patients (449 men and 1,809 women) and 22,580 healthy participants (4,490 men and 18,090 women) who were individually matched by age, gender, and enrollment year. In-person interviews were conducted with a structured questionnaire to obtain epidemiologic data. Clinicopathologic features of the patients were obtained by chart reviews. Odds ratios (ORs) and 95% confidence intervals (95%CI) were estimated using conditional regression models. RESULTS:While light or moderate drinking behavior was related to a reduced risk of DTC, acute heavy alcohol consumption (151 g or more per event or on a single occasion) was associated with increased risks in men (OR = 2.22, 95%CI = 1.27-3.87) and women (OR = 3.61, 95%CI = 1.52-8.58) compared with never-drinkers. The consumption of alcohol for 31 or more years was a significant risk factor for DTC for both men (31-40 years: OR = 1.58, 95%CI = 1.10-2.28; 41+ years: OR = 3.46, 95%CI = 2.06-5.80) and women (31-40 years: OR = 2.18, 95%CI = 1.62-2.92; 41+ years: OR = 2.71, 95%CI = 1.36-5.05) compared with never-drinkers. The consumption of a large amount of alcohol on a single occasion was also a significant risk factor, even after restricting DTC outcomes to tumor size, lymph node metastasis, extrathyroidal extension and TNM stage. CONCLUSION:The findings of this study suggest that the threshold effects of acute high-dose alcohol consumption and long-term alcohol consumption are linked to an increased risk of DTC.

BACKGROUND:BRAFV600E is the most common mutation in papillary thyroid carcinoma (PTC), and it is associated with high-risk prognostic factors. However, the significance of the BRAF mRNA level in PTC remains unknown. We evaluated the significance of BRAF mRNA expression level by analyzing PTC data from The Cancer Genome Atlas (TCGA) database. METHODS:Data from 499 patients were downloaded from the TCGA database. After excluding other PTC variants, we selected 353 cases of classic PTC, including 193 cases with BRAFV600E and 160 cases with the wild-type BRAF. mRNA abundances were measured using RNA-Seq with the Expectation Maximization algorithm. RESULTS:The mean BRAF mRNA level was significantly higher in BRAFV600E patients than in patients with wild-type BRAF (197.6 vs. 179.3, p = 0.031). In wild-type BRAF patients, the mean BRAF mRNA level was higher in cases with a tumor > 2 cm than those with a tumor ≤ 2.0 cm (189.4 vs. 163.8, p = 0.046), and was also higher in cases with lymph node metastasis than in those without lymph node metastasis (188.5 vs. 157.9, p = 0.040). Within BRAFV600E patients, higher BRAF mRNA expression was associated with extrathyroidal extension (186.4 vs. 216.4, p = 0.001) and higher T stage (188.1 vs. 210.2, p = 0.016). CONCLUSIONS:A higher BRAF mRNA expression level was associated with tumor aggressiveness in classic PTC regardless of BRAF mutational status. Evaluation of BRAF mRNA level may be helpful in prognostic risk stratification of PTC.

Background. Laparoscopic lateral transperitoneal adrenalectomy (LTA) has been the standard method for resecting benign adrenal gland tumors. Recently, however, laparoscopic posterior retroperitoneal adrenalectomy (PRA) has been more popular as an alternative method. This systematic review evaluates current evidence on adrenalectomy techniques, comparing laparoscopic LTA with PRA and laparoscopic adrenalectomy with robotic adrenalectomy. Methods. PubMed, Embase, and ISI Web of Knowledge databases were searched systematically for studies comparing surgical outcomes of laparoscopic LTA versus PRA and laparoscopic versus robotic adrenalectomy. The studies were evaluated according to the PRISMA statement. Results. Eight studies comparing laparoscopic PRA and LTA showed that laparoscopic PRA was superior or at least comparable to laparoscopic LTA in operation time, blood loss, pain score, hospital stay, and return to normal activity. Conversion rates and complication rates were similar. Six studies comparing robotic and laparoscopic adrenalectomy found that outcomes and complications were similar. Conclusion. Laparoscopic PRA was more effective than LTA, especially in reducing operation time and hospital stay, but there was no evidence showing that robotic adrenalectomy was superior to laparoscopic adrenalectomy. Cost reductions and further technical advances are needed for wider application of robotic adrenalectomy.

Purpose: This study aimed to investigate the effectiveness of a novel wound protector in enhancing the cosmetic outcomes of thyroidectomy. Material and methods: This multicenter, double-blinded randomized controlled trial enrolled 129 patients undergoing open thyroidectomy. The patients were divided into a wound protector group and a control group. Subjective patient assessments were conducted, measuring wound satisfaction, pain, and itchiness. Additionally, blinded observers evaluated scars using the Vancouver Scar Scale. Results: The Vancouver Scar Scale revealed significant advantages for the wound protector group, demonstrating improvements in pigmentation (P=0.002), vascularity (P= 0.014), pliability (P =0.001), and height (P=0.001). Conclusion: The thyroid wound protector offers a potential to improve postoperative cosmetic outcomes. Further research is warranted to explore patient experiences and optimize the application of this innovative wound protector across diverse surgical contexts. [ABSTRACT FROM AUTHOR]